当归超临界提取物和酚酸类成分配伍预防结直肠癌作用研究Colorectal cancer preventive effect of combined administration of phenolic acids and supercritical extracts from Angelica sinensis
彭宇;赵博琛;康倩;刘葭;陈柽;李冰韶;谢远平;吴清;
PENG Yu;ZHAO Bo-chen;KANG Qian;LIU Jia;CHEN Cheng;LI Bing-shao;XIE Yuan-ping;WU Qing;School of Chinese Material Medica,Beijing University of Chinese Medicine;
摘要(Abstract):
该文旨在考查当归酚酸类提取物配伍低、中、高3个剂量的当归超临界提取物在氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)小鼠结直肠癌模型上的癌症预防作用。采用AOM单剂量注射启动癌症发生,口服DSS诱导小鼠慢性结直肠炎发生,促进肿瘤发展,模拟人类炎症相关的结直肠癌的发生发展全过程。在结直肠癌模型启动阶段,当归酚酸以1 g·kg~(-1)体质量剂量口服给药,在模型发展阶段,低、中、高3个剂量(15,30,60 mg·kg~(-1)体质量)的当归超临界提取物对小鼠进行灌胃给药,在第12周实验结束时取出小鼠结直肠组织,计算肿瘤发生率,测量肿瘤的体积,进行组织病理学分析,免疫组化考察肿瘤组织中PCNA和8-羟基鸟嘌呤表达,Western blot法分析肿瘤组织中γ-H2AX,i NOS和COX-2表达量。结果显示,当归酚酸配伍超临界提取物能够有效抑制肿瘤的发生发展,降低结直肠组织中细胞增殖活性,减轻DNA损伤,抑制炎性反应,并且表现出一定的剂量依赖性。其作用机制可能与当归酚酸类提取物在模型前期抵抗AOM造成的DNA氧化损伤,当归超临界提取物在模型后期抑制DSS诱导的慢性炎性反应相关。综上,当归酚酸配伍超临界提取物对于AOM/DSS诱导的小鼠结直肠癌的发生发展具有一定的干预作用,具有开发成癌症化学预防药物的潜力。
This study aimed to investigate the colorectal cancer preventive effect of the combined administration of phenolic acids and supercritical extracts from Angelica sinensis. The AOM/DSS model in mice was adopted. Phenolic acids were administrated orally in the initial stage of the model at a dose of 1 g·kg~(-1) BW,which was combined withtherectal administration with three doses of supercritical extracts( 15,30,60 g·kg~(-1) BW). PCNA,8-oxoguaine,γ-H2 AX,i NOS and COX-2 were tested by immunohistochemistry and Western blot assays. The results showed that the combined administration of phenolic acids and supercritical extracts from A.sinensis suppressed the tumor growth and cell proliferation,and DNA damages and inflammatory responses were reduced in a dose-dependent manner. These results indicate that the combined administration of phenolic acids and supercritical extracts from A. sinensis have a certain effect in preventing carcinogenesis.
关键词(KeyWords):
当归;酚酸;超临界提取;癌症预防;结直肠癌
Angelica sinensis;phenolic acid;supercritical extract;cancer prevention;colorectal cancer
基金项目(Foundation): 国家自然科学基金项目(81773915)
作者(Author):
彭宇;赵博琛;康倩;刘葭;陈柽;李冰韶;谢远平;吴清;
PENG Yu;ZHAO Bo-chen;KANG Qian;LIU Jia;CHEN Cheng;LI Bing-shao;XIE Yuan-ping;WU Qing;School of Chinese Material Medica,Beijing University of Chinese Medicine;
Email:
DOI: 10.19540/j.cnki.cjcmm.2018.0048
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- 当归
- 酚酸
- 超临界提取
- 癌症预防
- 结直肠癌
Angelica sinensis - phenolic acid
- supercritical extract
- cancer prevention
- colorectal cancer
- 彭宇
- 赵博琛
- 康倩
- 刘葭
- 陈柽
- 李冰韶
- 谢远平
- 吴清
PENG Yu- ZHAO Bo-chen
- KANG Qian
- LIU Jia
- CHEN Cheng
- LI Bing-shao
- XIE Yuan-ping
- WU Qing
- School of Chinese Material Medica
- Beijing University of Chinese Medicine
- 彭宇
- 赵博琛
- 康倩
- 刘葭
- 陈柽
- 李冰韶
- 谢远平
- 吴清
PENG Yu- ZHAO Bo-chen
- KANG Qian
- LIU Jia
- CHEN Cheng
- LI Bing-shao
- XIE Yuan-ping
- WU Qing
- School of Chinese Material Medica
- Beijing University of Chinese Medicine